Darzalex 1.800 mg solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

DARZALEX 1800mg injection solution

daratumumab

Read the entire leaflet carefully before you start receiving this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are possible side effects not listed in this leaflet. See section 4.

Leaflet contents

1. What DARZALEX is and what it is used for
2. What you need to know before receiving DARZALEX
3. How DARZALEX is administered
4. Possible side effects
5. How to store DARZALEX
6. Contents of the pack and other information

1. What DARZALEX is and what it is used for

What DARZALEX is

DARZALEX is a medicine that contains the active substance daratumumab. It belongs to a group of medicines called "monoclonal antibodies". Monoclonal antibodies are proteins that are designed to recognize and bind to specific targets in the body. Daratumumab is designed to bind to specific abnormal blood cells in the body, enabling the immune system to destroy them.

What DARZALEX is used for

DARZALEX is used in adults aged 18 years or older who have a type of cancer called "multiple myeloma". This is a cancer of the bone marrow.

DARZALEX is used in adults aged 18 years or older who have a blood and bone marrow disorder called "smoldering multiple myeloma" that may progress to multiple myeloma.

DARZALEX is also used in adults aged 18 years or older who have a blood disorder called "AL amyloidosis". In AL amyloidosis, abnormal blood cells produce excessive amounts of abnormal proteins that are deposited in various organs, causing them to malfunction.

2. What you need to know before you start receiving DARZALEX

Do not receive DARZALEX

• if you are allergic to daratumumab or to any of the other ingredients of this medicine (listed in section 6).

You must not receive DARZALEX if you meet the above criterion. If you are unsure, consult your doctor or nurse before starting DARZALEX.

Warnings and precautions

Talk to your doctor or nurse before you start receiving DARZALEX.

Infusion-related reactions

DARZALEX is administered as a subcutaneous injection using a small needle to inject the medicine under your skin. Before and after each injection, you will be given medicines to help reduce the likelihood of infusion-related reactions (see the section “Medicines administered during treatment with DARZALEX” in section 3). These reactions occur mostly with the first injection, and most happen on the day of the injection. If you have previously experienced an infusion-related reaction, it is less likely to happen again. However, delayed reactions may occur up to 3–4 days after the injection. If you have a severe reaction after the injection, your doctor may decide not to continue using DARZALEX.

In some cases, you may experience a severe allergic reaction, which may include swelling of the face, lips, mouth, tongue, or throat, difficulty swallowing or breathing, or an itchy rash (urticaria). See section 4.

Immediately inform your doctor or nurse if you experience any of the infusion-related reactions or related symptoms listed at the beginning of section 4. If you experience infusion-related reactions, you may need additional medicines to treat your symptoms, or the injections may need to be stopped. Once these reactions have resolved or improved, the injection may be restarted.

Reduction in blood cell counts

DARZALEX may reduce the number of white blood cells—cells that help fight infections—and of other blood cells called platelets, which help blood to clot. Inform your healthcare provider if you develop any signs of infection such as fever, or any signs of low platelet counts such as bruising or bleeding.

Blood transfusions

If you need a blood transfusion, a blood test will first be performed to determine your blood group. DARZALEX may affect the results of this blood test. Inform the person performing the test that you are receiving DARZALEX.

Hepatitis B

Inform your doctor if you have ever had, or may currently have, a hepatitis B virus infection. This is because DARZALEX could cause reactivation of the hepatitis B virus. Your doctor will monitor you for signs of this infection before, during, and for some time after treatment with DARZALEX. Immediately inform your doctor if you develop worsening fatigue or notice yellowing of the skin or the whites of the eyes.

Children and adolescents

Do not administer DARZALEX to children or adolescents under 18 years of age, as it is unknown how the medicine will affect them.

Other medicines and DARZALEX

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines. This includes medicines obtained without a prescription and herbal medicines.

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving this medicine.

If you become pregnant during treatment with this medicine, inform your doctor or nurse immediately. You and your doctor will decide whether the benefit of receiving the medicine outweighs the risk to the fetus.

Contraception

Women receiving DARZALEX should use an effective method of contraception during treatment and for 3 months after treatment ends.

Breast-feeding

You and your doctor will decide whether the benefit of breast-feeding outweighs the risk to your baby, as this medicine may pass into breast milk and it is unknown how it may affect the baby.

Driving and use of machines

You may feel tired after using DARZALEX, which may affect your ability to drive or operate machinery.

DARZALEX subcutaneous injectable solution contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per 15 ml, i.e., essentially “sodium-free.”

DARZALEX subcutaneous injectable solution contains sorbitol

Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to certain sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic condition in which a person cannot break down fructose, consult your doctor before receiving this medicine.

DARZALEX subcutaneous injectable solution contains polysorbate

This medicine contains 0.4 mg of polysorbate 20 per ml, equivalent to 6.0 mg per 15 ml vial. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How DARZALEX is administered

Dose administered

The dose of DARZALEX subcutaneous injection solution is 1800 mg.

DARZALEX may be given alone or in combination with other medicines used to treat multiple myeloma, or with other medicines used to treat AL amyloidosis. DARZALEX is usually administered as follows:

• once a week for the first 8 weeks
• then once every 2 weeks for 16 weeks
• after this, once every 4 weeks as long as the disease does not worsen.

When DARZALEX is administered together with other medicines, your doctor may adjust the time between doses and the number of treatments you receive.

How the medicine is administered

A doctor or nurse will administer DARZALEX to you as an injection under the skin (subcutaneous injection) over approximately 3 to 5 minutes. It is administered in the abdominal area (abdomen), not in other areas of the body, and not in areas of the abdomen where the skin is red, bruised, tender, hardened, or scarred.

If you experience pain during the injection, the doctor or nurse may pause the injection and administer the remainder in another area of your abdomen.

Medicines administered during DARZALEX treatment

You may be given medicines to reduce the likelihood of developing herpes zoster.

Before each DARZALEX injection, you will be given medicines to help reduce the risk of infusion-related reactions. These may include:

• medicines to treat allergic reactions (antihistamines)
• medicines to treat inflammation (corticosteroids)
• medicines to treat fever (such as paracetamol).

After each DARZALEX injection, you will be given medicines (such as corticosteroids) to reduce the risk of infusion-related reactions.

People with breathing problems

If you have breathing problems, such as asthma or chronic obstructive pulmonary disease (COPD), you will be given inhaled medicines to help treat breathing difficulties:

• medicines to keep the airways of the lungs open (bronchodilators)
• medicines to reduce inflammation and irritation in the lungs (corticosteroids).

If you receive more DARZALEX than you should

A doctor or nurse will administer this medicine to you. In the unlikely event that an excessive dose is administered (overdose), your doctor will monitor you for any adverse effects.

If you miss your appointment to receive DARZALEX

It is very important that you attend all your appointments to ensure the treatment is effective. If you miss an appointment, schedule another one as soon as possible.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone gets them.

Reactions related to infusion

Inform your doctor or nurse immediately if, during the 3–4 days after the injection, you experience any of the following symptoms. You may need additional medicines, or it may be necessary to interrupt or stop the injections.

These reactions include the following symptoms:

Very common (may affect more than 1 in 10 people):

• chills
• sore throat, cough
• feeling sick (nausea)
• vomiting
• itching, runny or stuffy nose
• difficulty breathing or other breathing problems

Common (may affect up to 1 in 10 people):

• chest discomfort
• dizziness or vertigo (hypotension)
• itching
• wheezing

Rare (may affect up to 1 in 1,000 people):

• severe allergic reaction, which may include swelling of the face, lips, mouth, tongue or throat, difficulty swallowing or breathing, or an itchy rash (urticaria). See section 2.
• eye pain
• blurred vision

If you experience any of the infusion-related reactions listed above, inform your doctor or nurse immediately.

Injection site reactions

Skin reactions may occur at or near the injection site (local reactions), including injection site reactions with DARZALEX subcutaneous injectable solution. These reactions are common (may affect up to 1 in 10 people). Symptoms at the injection site may include redness of the skin, itching, swelling, pain, bruising, rash, and bleeding.

Other adverse effects

Very common (may affect more than 1 in 10 people):

• fever
• feeling very tired
• diarrhoea
• constipation
• abdominal pain
• decreased appetite
• difficulty sleeping
• headache
• nerve damage which may cause tingling, numbness or pain
• rash
• muscle spasms
• muscle and joint pain (including back pain and chest muscle pain)
• swollen hands, ankles or feet
• weakness
• lung infection (pneumonia)
• bronchitis
• respiratory tract infection, such as in the nose, sinuses or throat
• low number of red blood cells, which carry oxygen in the blood (anaemia)
• low number of white blood cells, which help fight infections (neutropenia, lymphopenia, leucopenia)
• low number of a type of blood cell called platelets, which help the blood to clot (thrombocytopenia)
• low potassium levels in the blood (hypokalaemia)
• COVID-19

Common (may affect up to 1 in 10 people):

• irregular heartbeat (atrial fibrillation)
• fluid accumulation in the lungs, leading to difficulty breathing
• urinary tract infection
• serious infection throughout the body (sepsis)
• dehydration
• high blood sugar levels
• low calcium levels in the blood
• low levels of antibodies called 'immunoglobulins' in the blood, which help fight infections (hypogammaglobulinaemia)
• feeling dizzy
• fainting
• chills
• itching
• unusual sensations in the skin (such as tingling or prickling)
• inflammation of the pancreas

Uncommon (may affect up to 1 in 100 people):

• inflammation of the liver (hepatitis)
• infection with a type of herpes virus (cytomegalovirus infection)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of DARZALEX

DARZALEX subcutaneous injectable solution will be stored at the hospital or clinic.

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep in the original packaging to protect from light.

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will dispose of any unused medicines. This helps protect the environment.

6. Contents of the pack and other information

Composition of DARZALEX

• The active substance is daratumumab. One ml of solution contains 120 mg of daratumumab. Each 15 ml vial of injectable solution contains 1800 mg of daratumumab.
• The other components are recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol (E420), and water for injections (see section 2, “DARZALEX contains sodium and sorbitol”).

Nature and contents of the container

DARZALEX subcutaneous injectable solution is a liquid, colourless to yellow in appearance.

DARZALEX subcutaneous injectable solution is supplied in a carton containing 1 single-dose glass vial.

Marketing Authorization Holder

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer

Janssen Biologics B.V.
Einsteinweg 101
NL-2333 CB Leiden
The Netherlands

For more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

This information is intended for healthcare professionals only:

DARZALEX subcutaneous injection solution must be administered by a healthcare professional.

To prevent medication errors, it is important to check the vial labels to ensure that the correct formulation (intravenous or subcutaneous formulation) is being administered and that the prescribed dose is given to the patient as specified. DARZALEX injectable solution must be administered only by subcutaneous injection at the specified dose. The DARZALEX subcutaneous formulation is not indicated for intravenous administration.

DARZALEX subcutaneous injectable solution is for single use only and is supplied ready-to-use.

• DARZALEX subcutaneous injectable solution is compatible with syringes made of polypropylene or polyethylene; with subcutaneous infusion sets made of polypropylene, polyethylene, or polyvinyl chloride (PVC); and with stainless steel injection and transfer needles.
• DARZALEX subcutaneous injectable solution should be a solution ranging from transparent to opalescent, from colourless to yellow. Do not use if it contains opaque particles, discolouration, or foreign particles.
• Remove the vial of DARZALEX subcutaneous injectable solution from the refrigerated storage (2 °C – 8 °C) and allow it to equilibrate to room temperature (15 °C–30 °C). The unopened vial may be stored at room temperature and light conditions for up to 24 hours in the original packaging to protect it from light. Protect from direct sunlight. Do not shake.
• Prepare the administration syringe under controlled, validated aseptic conditions. Withdraw 15 ml from the vial using a syringe and an 18G–22G transfer needle with regular bevel to minimize the risk of particulate shedding upon stopper puncture. Insert the needle into the vial at a 90° angle within the stopper ring, and minimize the number of punctures to prevent stopper fragmentation. Inspect the syringe contents to ensure absence of particles, discolouration, or other foreign matter.
• To avoid needle blockage, attach the hypodermic needle or subcutaneous infusion set to the syringe immediately before injection.

Storage of the prepared syringe

• If the DARZALEX syringe is not used immediately, store the DARZALEX solution for up to 24 hours under refrigerated conditions followed by up to a maximum of 12 hours at 15 °C–25 °C and room light. If stored in the refrigerator, allow the solution to reach room temperature before administration.

Administration

• Inject 15 ml of DARZALEX subcutaneous injectable solution into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3–5 minutes. Do not inject DARZALEX subcutaneous injectable solution into other body areas, as no data are available.
• For subsequent injections, alternate the administration sites.
• DARZALEX subcutaneous injectable solution must never be injected into areas of skin showing redness, bruising, tenderness, induration, or scarring.
• Pause or reduce the administration rate if the patient experiences pain. If pain does not resolve with reduced injection speed, the remainder of the dose may be administered at a second injection site on the opposite side of the abdomen.
• During treatment with DARZALEX subcutaneous injectable solution, do not administer other medications by subcutaneous route at the same site as DARZALEX.
• Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations.

Traceability

In order to improve traceability of biological medicines, the name and batch number of the administered medicine should be clearly documented.